tbuckley/cabot-search huggingface dataset:
AB0571 DERIVATION AND INDEPENDENT VALIDATION OF THE LUPUS ARTHRITIS AND MUSCULOSKELETAL DISEASE ACTIVITY SCORE (LAMDA): A MORE SENSITIVE, SPECIFIC AND RESPONSIVE TOOL FOR LUPUS ARTHRITIS
Authors: K. Mahmoud, A. Zayat, M. Y. MD Yusof, L. S. Teh, S. Khan, C. S. Yee, D. D’cruz, N. Ng, D. Isenberg, C. Ciurtin, P. G. Conaghan, P. Emery, C. J. Edwards, E. Hensor, E. Vital
Journal: Annals of the Rheumatic Diseases (2022)

Background The MSK components of the BILAG and SLEDAI have limited sensitivity, specificity and responsiveness. Objectives To develop a better disease activity tool for MSK lupus. Methods “LAMDA” was derived using data from the multicentre USEFUL study (PMID:33792659); 133 patients with inflammatory MSK pain received intramuscular depomedrone then were assessed for 66/68 SJC/TJC, BILAG-2004, SLEDAI-2K, physician MSK-VAS, inflammatory markers, patient pain and disease-activity-VAS and MSK-ultrasound. Baseline variables were modelled against US using penalized (Lasso) regression. For validation we evaluated: (i) responsiveness at week 6 in USEFUL and (ii) association with quality of life and treatment decision in an independent study (n=100). Results LAMDA was a composite of SJC, patient-MSK-pain-VAS, physician-MSK-disease-activity-VAS and ESR ranging from 0 to 26.5. Response effect size was greater for the LAMDA (0.37) than the BILAG-MSK (0.31), SLEDAI-MSK (0.27) and total US score (0.33). With active US at baseline, LAMDA’s effect size was 0.42. In the validation study LAMDA score correlated with better physical function (R = -0.49, p&lt;0.001), pain (R = -0.44, p=0.002) and Burden to Others (R = -0.38, p=0.009). LAMDA was higher when therapy was increased (mean (95% CI) difference 12.9 (5.8, 19.9), p&lt;0.001). Conclusion LAMDA is a continuous disease activity instrument for MSK lupus that is sensitive to imaging-synovitis without swelling, more responsive than other instruments and correlates with quality of life and treatment decision. LAMDA may improve the ability of clinicians to monitor and treat MSK lupus, and determine the efficacy of therapies in clinical trials. Acknowledgements Funding: Lupus UK and NIHR Disclosure of Interests Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Lee-Suan Teh: None declared, Shah Khan: None declared, Chee-Seng Yee: None declared, David D’Cruz: None declared, Nora Ng: None declared, David Isenberg: None declared, Coziana Ciurtin: None declared, Philip G Conaghan: None declared, Paul Emery: None declared, Christopher John Edwards: None declared, Elizabeth Hensor: None declared, Edward Vital Speakers bureau: GSK, AstraZeneca, Consultant of: GSK, AstraZeneca, Roche, Aurinia, Lilly, ILTOO, Novartis, Grant/research support from: AstraZeneca, Sandoz
POS1352 A PROSPECTIVE, ONE-YEAR FOLLOW-UP STUDY OF PATIENTS NEWLY DIAGNOSED WITH NEUROSARCOIDOSIS
Authors: K. E. Byg, Z. Illes, T. Sejbaek, N. Nguyen, S. Möller, K. Lambertsen, H. Nielsen, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2022)

Background Sarcoidosis is a granulomatous inflammation of unknown etiology. Neurosarcoidosis (NS) occurs in 5–10% of patients with sarcoidosis and is a severe manifestation of sarcoidosis. The clinical presentation is heterogeneous and depends on the inflammation within the nervous system. Objectives This study aimed to describe NS patients and their clinical course of treatment. Our outcomes were changes in 1) enhancing lesions on MRI of the central nervous system (CNS), 2) cerebrospinal fluid (CSF), 3) disability and dependency in daily activities assessed by the modified Rankin Scale (mRS), 4) cognitive function assessed by the Symbol Digit Modality Test (SDMT), 5) quality of life assessed by Short-Form 36 Health Survey (SF-36), 6) fatigue assessed by Fatigue Assessment Scale (FAS), and 7) depression measured by Beck Depression Inventory-II (BDI-II). Methods In this observational cohort study with a one-year follow-up, we consecutively recruited NS patients (N=20), not including patients with polyneuropathy, from the Departments of neurology and rheumatology at Odense University Hospital between January 2016 and August 2020. Patients were examined clinically, with questionnaires and MRI at baseline (V) and after three months (V3), six months (V6), and 12 months (V12). Cerebrospinal fluid (CSF) was examined at baseline, V6, and V12. Results The median age was 51.6 years, and the median duration of sarcoidosis symptoms was 8 months before inclusion. At baseline, 60% of NS patients had headache, followed by vertigo (55%) and tinnitus (50%). Objective neurological findings were peripheral sensory signs (50%), peripheral motor signs (40%), and cranial nerve involvement (30%). At V12, there were significant improvements in vertigo (p=0.03), cranial nerve involvement (p=0.03), and joint symptoms (p=0.03). At baseline, 60% of patients had abnormal findings on MRI of CNS. During the study, the number of contrast-enhancing lesions on MRI decreased significantly (p&lt;0.0001). The mRS declined significantly from mean (SD) 3.0 (0.8) at baseline to 1.8 (1.1) at V12 (p&lt;0.0001), and 75% of patients experienced clinically important improvement (mRS≥1). The SDMT score improved significantly from mean (SD) 38 (9) at baseline to 45 (12) at V12 (p&lt;0.0001). The SF-36 Physical (PCS) and Mental Component Summary scores (MCS) improved significantly from baseline: PCS mean (SD) 35 (11) to 41 (12) at V12 (p=0.003) and MCS mean (SD) 41(9) to 48 (10) at V12 (p=0.03). The proportions of patients with substantial fatigue (75%) and high depression score (35%) were unchanged. Conclusion One year of immunosuppression in NS patients improved several outcomes, and 75% of patients experienced clinically important improvement. Disclosure of Interests None declared
POS0450 TEMPORAL MIGRATION OF IMMUNE CELLS FROM PSORIATIC SKIN TO JOINTS INITIATING SYNOVIAL INFLAMMATION IN PSORIATIC ARTHRITIS
Authors: M. G. Raimondo, S. Rauber, C. Xu, H. Mohammadian, M. Vogg, C. G. Anchang, A. Rius Rigau, M. Luber, H. Labinsky, A. Soare, J. H. W. Distler, U. Fearon, D. Veale, M. Sticherling, J. D. D. Cañete, G. Schett, A. Ramming
Journal: Annals of the Rheumatic Diseases (2022)

Background Spreading of inflammation from skin to joint is a key question behind the pathogenesis of psoriatic arthritis (PsA). Psoriasis (PsO), being one of the most prevalent skin diseases, usually anticipates joint manifestations, suggesting spreading of skin to joint disease, which happens in about 30% of the patients with psoriasis. 1 To date, it is still obscure why the inflammatory process in some patients with PsO remains restrained to the skin, whereas in other patients it extents to tendons and joints. Objectives Using a pre-clinical model of PsA, we aimed to unveil the skin-joint axis, i.e. the spreading of psoriatic inflammation from the skin to the joints. Methods KAEDE transgenic mice expressing a photo-convertible fluorescent reporter were used to assess cell trafficking from inflamed skin to other organs in the mouse model of IL-23 overexpression (IL-23OE) induced PsA. Psoriatic skin lesions were irradiated with UV light to trigger the photoswitch from KAEDE GREEN to KAEDE RED . Migration to different organs was determined by flow cytometry. Imaging flow cytometry was used to characterize the type of cells migrating from the skin to the joints. Migrating cells were further characterized by single-cell RNA-sequencing (scRNAseq) and functional analyses. Results MRI imaging and histological evaluation of IL-23OE mice revealed skin inflammation preceding joint inflammation in both wild-type and KAEDE-transgenic mice. Specific leukocyte migration from the skin to the joints started shortly after the onset of skin inflammation and before onset of inflammation within the joints of KAEDE transgenic mice. No migration was observed in healthy control animals. Other organs such as spleen or lymph nodes showed no model-dependent migration. Imaging flow cytometry revealed that the cells migrating to the joints were predominantly CD45+ CD11b+ cells. ScRNAseq analysis of sorted KAEDE RED cells from inflamed joints confirmed that approximately 80% of the migrating cells were macrophages. Differential gene expression and pathway analysis revealed an imbalance between pro- and anti-inflammatory macrophages in the joints of experimental psoriatic arthritis. Conclusion We describe IL-23-mediated migration of skin-derived macrophages from the skin to the joints during the onset of experimental psoriatic arthritis. This process may explain the spreading from psoriatic skin to joint disease as these cells foster the development by local cytokine production once arrived in the joints. References [1]Veale, D.J. &amp; Fearon, U. The pathogenesis of psoriatic arthritis. Lancet 391 , 2273-2284 (2018). Disclosure of Interests None declared.
AB0273 IDENTIFICATION OF RED FLAGS FOR INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: P. Conigliaro, E. De Martino, E. Cela, P. Triggianese, M. S. Chimenti, A. Luciano, M. Chiocchi, J. Ora, F. Cavalli, F. Garaci, R. Floris, P. Rogliani, A. Bergamini
Journal: Annals of the Rheumatic Diseases (2022)

Background Interstitial lung disease (ILD) in Rheumatoid Arthritis (RA) can be subclinical or underestimated. Data from the literature report male sex, seropositivity and old age as known risk factors for ILD in RA. However, the correct timing for referral to pneumologists and eligibility for CT chest scan is undefined. Objectives To identify potential red flags of ILD diagnosis for referral to a multidisciplinary team analyzing clinical and radiological findings associated with the establishment of ILD. Methods Retrospective study on CT chest scan from RA patients evaluated and categorized into usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and unclassifiable RA-ILD (Un-ILD), by two radiologists. RA-ILD was diagnosed by two pneumologists considering radiological and clinical factors. Results 80 CT chest scans from RA patients (F 59, age 66,6 ± 11,4, disease duration 7,8 ± 4,4) were evaluated. 36,5% of patients had performed CT-chest scan for suspect of ILD, 11,2% for probable pulmonary infection, 8,7% for oncological screening or follow up, 13,7% for COPD disease, 8,7% for screening or active TBC, 3,7% for screening or previous pleuritis and 17,5% for other reasons. A RA-ILD pattern was identified in 35% of patients, with a defined UIP pattern in 17,8%, a defined NSIP pattern in 42,8% and a 39,3% of Un-ILD, while 65% of patients had a non-ILD lung involvement by CT-scan. The mean age at ILD diagnosis was 67,2 years and the mean time between RA diagnosis and onset of ILD symptoms was 7,4 years. In the multivariate analysis female sex (HR=0,33; p=0,006) and disease duration (HR=0,8; p=0,06) were protective factors for ILD diagnosis. Age (HR=1,1; p=0,03), use of leflunomide (HR=10,1; p=0,03) were negative prognostic factors for ILD. Pulmonary clinical symptoms as dry cough (HR=17,6; p=0,02), bibasilar inspiratory crackles (HR=11,5; p=0,01) and pleural rubs (HR=18,1; p=0,03) predicted ILD while negative predictors were the presence of linear opacities (HR=99,9; p=0,006), interstitial abnormalities (HR=12,1; p=0,07) and cystic areas (HR=33,3; p=0,06) at chest CT scan. Conclusion In our cohort the first ILD symptom appeared 7.4 years after RA diagnosis. Clinical variables and radiological abnormalities were identified as highly predictive of ILD diagnosis and may represent red flags for an early diagnosis and referral to pneumologists and radiologists in a multidisciplinary approach. Disclosure of Interests None declared
AB0972 Impact of obesity on clinical manifestations in patients with osteoarthritis of the knee
Authors: N. Zhuravleva, T. Smirnova, O. Sharapova, L. Gerasimova, L. Markelova
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To determine the influence of obesity on clinical parameters in patients with knee osteoarthritis (OA) in comparison with patients with OA with normal body weight. Methods Overall 72 patients with OA were studied, 28 (39.8%) male and 44 (61.1%) female; mean age was 51.3±7.5 years and the duration of disease was 11.2±5,3 years. The diagnosis of OA was made according to the ACR criteria. Anthropometric data were assessed by height, body weight, waist and hip circumference, body mass index (BMI). Clinical and instrumental studies of OA revealed monoarthrosis in 2 (2.8%), oligoarthrosis in 32 (44.4%) and polyosteoarthrosis in 38 (52.8%) patients. Visual analogue scale (VAS) in centimetres (cm) was used to assess pain, Lequesne and WOMAC indices were determined. Synovitis was documented on the basis of an ultrasound examination of the joints. Patients were divided into 2 groups according to BMI: BMI&lt;24.9 kg/m 2 , n=22 (no obesity); BMI&gt;30kg/m 2 , with signs of grade 1-2-3 obesity, n=50. Results OA patients with obesity had higher WOMAC and Lequesne index values than OA patients with normal weight (5.8±1.2 cm and 13.8±1.1 points versus 1.75±0.7 cm and 2.9±0.5 points, respectively, p&lt;0.05). WOMAC parameters in overweight patients were significantly higher than in non-obese patients (31.2±5.9 vs. 9.7±2.7, respectively, p&lt;0.05 for the above parameters). There was a direct correlation (p&lt;0.05) between the severity of OA and increased BMI. Radiological changes of the joints in patients without obesity were stage I (60.6%) in 14 (60.6%), stage II in 7 (34.8%) and stage III in 1 (4.5%) patient. Grade I obesity was noted in 8 (16.0%), Grade II in 22 (44.0%), Grade III in 18 (36.0%), Grade IV in 2 (4.0%) patients. Inadequate joint function (NFS) grade I was in 16 (72.7%), II in 4 (18.2%), III in 2 (19.1%) patients with normal body weight, with NFS grade II (26 - 52%) and III (18-36%) predominating with obesity, grade I in 6 (12.0%). Synovitis was diagnosed in 37 (74.0%) with elevated BMI, significantly higher than in non-obese patients in 7 (31.8%). On the course: rapid progressive OA was seen more frequently in 11 obese patients (22. 0%) than in non-obese patients (4.5%); there was a direct correlation between the VAS pain index, Lequesne index and WOMAC index (r=0.5, p&lt;0.05; r=0.4, p&lt;0.05; r=0.45 p&lt;0.05 respectively). Conclusion Overweight in patients with OA was associated with greater joint destruction and functional impairment of the joints, progressive course and pain syndrome, including secondary synovitis. Disclosure of Interests None declared
AB1275 SUGGESTED APPROACH TO UBA1 GENE MUTATION TESTING IN PATIENTS WITH SUSPECTED VEXAS SYNDROME
Authors: K. Pavelcova, B. Stiburkova, V. Balajková, M. Belickova, C. Salek, M. Vostry, H. Mann, J. Vencovský
Journal: Annals of the Rheumatic Diseases (2022)

Background VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently identified autoinflammatory disease caused by de novo somatic mutations in the X-linked gene UBA1 (1). This disease is clinically characterized by inflammatory symptoms and bone marrow failure (2). Objectives The aim of our study was to identify genetic variants associated with VEXAS syndrome and to design an algorithm for detection of UBA1 gene mutations in patients with suspected VEXAS syndrome, which could be used for diagnosis. Methods We examined the UBA1 gene in 9 patients with clinically suspected VEXAS syndrome. We first focused on variants p.Met41Val, p.Met41Thr and p.Met41Leu with a known association with this disease (1). Samples of individual blood cell populations obtained by magnetic isolation were evaluated using RFLP, tetra-primer ARMS-PCR and Sanger sequencing. Subsequently, we analyzed the remaining exons of the UBA1 gene by Sanger sequencing. Results Using the above described method we have identified the previously described variants p.Met41Thr in two and p.Met41Leu in another two patients. In one patient, we discovered a new mutation p.Gly477Ala (c.1430G&gt;C) in exon 14 that has not yet been identified. The presence of these variants and their allelic forms (heterozygous / homozygous) varied between cell populations in individual patients. Conclusion The increasing number of reports suggests that VEXAS syndrome is not rare. In patients with clinical suspicion, typically UBA1 sequencing analysis of haematopoietic cells is performed in hot spot sites of p.Met41 in exon 3 only. Our results suggest that other variants, such as the newly identified p.Gly477Ala variant, may also be associated with clinical features of VEXAS syndrome. We propose that an extended analysis of all coding regions of the UBA1 gene may uncover other mutations with putative functional consequences. References [1]Beck DB, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020 Dec 31;383(27):2628-2638. doi: 10.1056/NEJMoa2026834. [2]Grayson PC, et al. VEXAS syndrome. Blood. 2021 Jul 1;137(26):3591-3594. doi: 10.1182/blood.2021011455. Acknowledgements Supported by MH CZ: DRO (Institute of Rheumatology, 00023728), RVO (VFN, 64165), DRO (IHBT, 00023736), grant NV18-03-00227, and grant NU21-05-00522. Disclosure of Interests None declared
AB0100 LONGER DISEASE DURATION OF RHEUMATOID ARTHRITIS IS ASSOCIATED WITH TNF RECEPTORS REDISTRIBUTION ON IMMUNOCOMPETENT CELLS AND CHANGES IN CELL SENSITIVITY TO CYTOKINE
Authors: A. Alshevskaya, J. Zhukova, J. Lopatnikova, O. Chumasova, N. Shkaruba, A. Sizikov, S. Sennikov
Journal: Annals of the Rheumatic Diseases (2022)

Background Longer duration of rheumatoid arthritis (RA) is associated not only with higher disease severity, but also with lower treatment efficacy including anticytokine therapy. One of key mechanisms implementing this is changing in expression of cytokines and their receptors actively involved in the pathological process, such as tumor necrosis factor (TNF). Objectives The aim of the study was to study the redistribution of TNF receptors in patients with different duration of RA and depending on the severity of the disease. Methods Subanalysis of RA patients with disease duration less than 10 years (Early RA group, n=34) and more than 10 years (Late RA group, n=30) was performed. Late RA patients had DAS-28 activity comparable with Early RA group (4.98 vs 4.69, p=0.68), but had higher radiological stage, higher levels of inflammatory markers, and more often received biologics and had systemic features. As a control group, data from 43 comparable healthy donors were used. Co-expression profile of TNF receptors type 1 and 2 (TNFR1/2) were assessed in main mononuclear subsets: T cells, B cells, monocytes, Tregs, T helpers, cytotoxic T cells. Dynamics of percentage of cells with different co-expression combination was estimated as well as receptors expression density per cell. Results The redistribution of receptors on 12 subpopulations of immune cells was studied. Two types of cell responses were associated with disease duration increase. The first trend was presented by monocytes, regulatory T cells and general pool of cytotoxic T cells and consisted in significant decrease in TNFR2 expression density with simultaneously increase of double-positive TNFR1+TNFR2+ cells percentage and decrease of TNFR1-TNFR2+ cells percentage with no changes in proportion of cells without receptors, as compared with health and with disease progression. The second type of response was presented by B cells, T cells, T helper naïve cells and activated T cells and represented a significant increase in TNFR1 expression density and increase of double-positive cells proportion compared to health without influence of disease duration and tendency to decrease in proportion of cells without receptors over time. Conclusion Two trends in the response of immunocompetent cells to changes in the level of TNF that occur during chronic inflammation in RA were established. These two trends demonstrate the reactive and adaptive mechanisms of immune cells actively involved in pathological process and are of significant interest for the possibilities of modulating cell sensitivity to the proapoptotic and proinflammatory effects of cytokine and for futher development of targeted RA therapy. Acknowledgements The study was supported by a grant from the Russian Science Foundation (project No. 20-75-10051) Disclosure of Interests None declared
AB0421 ASSESSEMENT OF LIVER STIFFNESS IN RHEUMATOID ARTHRITIS PATIENTS UNDER METHOTREXATE
Authors: W. Lahmar, M. Slouma, G. Mohamed, R. Dhahri, L. Metoui, I. Gharsallah, N. Abdelli
Journal: Annals of the Rheumatic Diseases (2022)

Background Methotrexate (MTX) is recommended as a first-line disease-modifying antirheumatic drug for treating rheumatoid arthritis (RA) in monotherapy or combinational therapy. A concern about MTX-related liver fibrosis in patients with rheumatoid arthritis (RA) is still unsolved. Objectives The aim of the study cutoff of cumulative dose discriminating patients with normal from those with abnormal liver stiffness. Methods We conducted a cross-sectional study including consecutive RA patients diagnosed according 2009 ACR-EULAR criteria. Liver stiﬀness (LS) was assessed by Fibroscan in the gastroenterology department by an experienced operator. The LS is measured in kilopascals (kPa). It is normal when &lt; 6.2 kPa. Above this rate it is considered pathological. Substantial liver fibrosis was defined as liver stiffness of greater than 8 kPa. We collected the following parameters: age, disease duration, disease activity assessed by DAS28, cumulated dose of MTX and duration of this treatment, and the body mass index (BMI). Patients underwent blood testing exploring hepatic function: alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl tansferase (GGT), total bilirubin (TB), albumin (ALB) and prothrombin time (PT). Statistical analysis was performed using SPSS software. Results There were 18 men and 36 women. The mean age was 51.9 + 11.49 [22-83]. The mean BMI was 27.27 + 3.40. The mean disease duration 8.08 + 6.28 years. The mean DAS28CRP was 3.96 + 1.49. The mean cumulative dose of MTX was 3670 + 3432.61mg and mean MTX duration was 55.75 + 50.89 months. The mean of LS was 4.6 + 1.64 kPa. The means of the liver blood tests are as follows: AST 20.83 + 8.58 UI/L, ALT 19.60 + 9.39 UI/L, ALP 84.65 + 38.68UI/L, TB 9.50 + 4.79 UI/L, GGT 25.88 + 14.26UI/L, ALB 35.19 + 5.47 g/L, PT 94.60 + 9.02. Eight patients had abnormal LS values and two patients had advanced liver fibrosis. However, hepatic blood tests (AST, ALT, GGT, TB, ALB, PT) were normal in these patients. A correlation was found between LS and following parameters: cumulative dose of MTX (r: 0.347, p: 0.013), the methotrexate duration (r: 0.363, p: 0.010) and total bilirubin rate (r:0.390, p: 0.005). Receiver Operator Curve (ROC) analysis showed the cutoff point of cumulative dose of MTX with the best accuracy in distinguishing patients with normal LS from those with LS higher than 6.2 kPA was 7330 mg, with a sensitivity of 50% and specificity of 91.3% (air under the curve (AUC) value: 0.732 (p=0.03). Conclusion Our study showed that LS correlated to both MTX duration and cumulative dose. Patients with a cumulative dose of MTX higher than 7330 mg required a close follow up of liver elastometry and monitoring of hepatic function. Disclosure of Interests None declared